On the other hand, an accelerated, or dose-dense, standard regimen led to significant increases in both endpoints, Cognetti reported at the annual San Antonio Breast Cancer Symposium.

But the key finding, Cognetti said, was that "5-FU should be deleted" from anthracycline-taxane combinations used after surgery for node-positive cancer.

The drug has been used for decades in other cancers and in other forms of breast cancer, but it has not been clear if it added anything as adjuvant treatment, combined with an anthracycline, for node-positive disease.

The study, dubbed GIM-2, tested a regimen of epirubicin and cyclophosphamide -- with or without 5-FU -- followed by paclitaxel. The regimens were given in either 3-week or 2-week cycles, so that patients were studied in one of four arms.

And the findings appear to have put the 5-FU issue to rest, commented C. Kent Osborne, MD, of Baylor College of Medicine in Houston, an SABCS co-chair who was not involved in the study.

In the U.S., he said, many centers have already stopped using the drug in combination with epirubicin and cyclophosphamide, he told MedPage Today.

"This demonstrates very clearly that it doesn't help," he said.

Cognetti and colleagues enrolled 2,091 patients between April 2003 and July 2006 and randomly assigned them to one of the four study arms.

The primary endpoint of the study, he said, was invasive DFS, but the researchers also studied OS and toxicity.

Overall, 86% of patients completed their assigned schedules, with no differences between the arms, he reported.

Patients in the dose-dense arms were more likely to have anemia and bone pain, he said, while those in the standard arms were more likely to report neutropenia.

After a median follow-up of 7 years, the researchers reported that a multivariate analysis showed that the dose-dense arms improved both DFS and OS. Specifically:

5-year relapse-free survival was 81% in the dose-dense arms and 76% for the standard arms, leading to a hazard ratio of 0.78 which was significant (P<0.002).

5-year OS was 94% in the dose-dense arms and 89% in the standard arms, yielding a hazard ratio of 0.69, which was significant (P=0.0001).

But adding 5-FU had "no effect on clinical outcomes" regardless of the dosing schedule, Cognetti said.

The accelerated dosing improved DFS regardless of clinical and pathological characteristics, he said. "It is the optimal option" for patients with early-stage node-positive patients, he said.

Cognetti reported no conflicts of interest or any external support for the study.

Osborne reported no conflicts of interest.

Reviewed by F. Perry Wilson, MD, MSCE Instructor of Medicine, Perelman School of Medicine at the University of Pennsylvania and Dorothy Caputo, MA, BSN, RN, Nurse Planner

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